{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T04:57:03Z","timestamp":1773896223017,"version":"3.50.1"},"reference-count":190,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This review explores the promising potential of repurposing type 2 diabetes (T2D) medications for the treatment of Parkinson\u2019s disease (PD), highlighting the shared pathophysiological mechanisms between these two age-related conditions, such as oxidative stress, mitochondrial dysfunction, and ferroptosis. The overlap suggests that existing diabetes drugs could target the common pathways involved in both conditions. Specifically, the review discusses how T2D medications, including metformin (Met), peroxisome-proliferator-activated receptor gamma (PPAR-\u03b3) agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, incretins, and dipeptidyl-peptidase 4 (DPP-4) inhibitors, can improve mitochondrial function, reduce neuroinflammation and oxidative stress, and potentially inhibit ferroptosis. The connection between ferroptosis and existing treatments, including diabetes medication, are only beginning to be explored. The limited data can be attributed also to the complexity of mechanisms involved in ferroptosis and Parkinson\u2019s disease and to the fact that the specific role of ferroptosis in Parkinson\u2019s disease pathogenesis has not been a primary focus until recent. Despite the promising preclinical evidence, clinical findings are mixed, underscoring the need for further research to elucidate these drugs\u2019 roles in neurodegeneration. Repurposing existing diabetes medications that have well-established safety profiles for Parkinson\u2019s disease treatment could significantly reduce the time and cost associated with drug development and could offer a more comprehensive approach to managing Parkinson\u2019s disease compared to treatments targeting a single mechanism.<\/jats:p>","DOI":"10.3390\/ijms26041516","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T09:36:05Z","timestamp":1739266565000},"page":"1516","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Targeting Ferroptosis in Parkinson\u2019s: Repurposing Diabetes Drugs as a Promising Treatment"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0229-1177","authenticated-orcid":false,"given":"Carmen","family":"Du\u021b\u0103","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corina","family":"Muscurel","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen Beatrice","family":"Dogaru","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0271-9946","authenticated-orcid":false,"given":"Irina","family":"Stoian","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,11]]},"reference":[{"key":"ref_1","unstructured":"Maserejian, N., Vinikoor-Imler, L., and Dilley, A. (2025, February 02). Estimation of the 2020 Global Population of Parkinson\u2019s Disease (PD). Available online: https:\/\/www.mdsabstracts.org\/abstract\/estimation-of-the-2020-global-population-of-parkinsons-disease-pd\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0140-6736(23)01301-6","article-title":"Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: A systematic analysis for the Global Burden of Disease Study 2021","volume":"402","author":"Ong","year":"2023","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1146\/annurev.neuro.28.061604.135718","article-title":"Molecular pathophysiology of Parkinson\u2019s disease","volume":"28","author":"Moore","year":"2005","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1080\/13543784.2020.1738383","article-title":"Brain insulin resistance: Role in neurodegenerative disease and potential for targeting","volume":"29","year":"2020","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Du\u021b\u0103, C., Muscurel, C., Dogaru, C.B., and Stoian, I. (2024). Ferroptosis-A Shared Mechanism for Parkinson\u2019s Disease and Type 2 Diabetes. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25168838"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1212\/WNL.0000000000005470","article-title":"Diabetes and Parkinson disease: A sweet spot?","volume":"90","author":"Das","year":"2018","journal-title":"Neurology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.2337\/diabetes.54.6.1615","article-title":"The Pathobiology of Diabetic Complications: A Unifying Mechanism","volume":"54","author":"Brownlee","year":"2005","journal-title":"Diabetes"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"135754","DOI":"10.1016\/j.neulet.2021.135754","article-title":"Therapies modulating insulin resistance in Parkinson\u2019s disease: A cross talk","volume":"749","author":"Sharma","year":"2021","journal-title":"Neurosci. Lett."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"319","DOI":"10.4239\/wjd.v13.i4.319","article-title":"Cognitive disorder and dementia in type 2 diabetes mellitus","volume":"13","author":"Ortiz","year":"2022","journal-title":"World J. Diabetes"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.2337\/db14-0568","article-title":"Insulin Action in Brain Regulates Systemic Metabolism and Brain Function","volume":"63","author":"Kleinridders","year":"2014","journal-title":"Diabetes"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/B978-0-12-385506-0.00004-1","article-title":"Chapter 4-Insulin, Synaptic Function, and Opportunities for Neuroprotection","volume":"Volume 98","author":"Rahman","year":"2011","journal-title":"Progress in Molecular Biology and Translational Science"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Hong, C.-T., Chen, K.-Y., Wang, W., Chiu, J.-Y., Wu, D., Chao, T.-Y., Hu, C.-J., Chau, K.-Y.D., and Bamodu, O.A. (2020). Insulin Resistance Promotes Parkinson\u2019s Disease through Aberrant Expression of \u03b1-Synuclein, Mitochondrial Dysfunction, and Deregulation of the Polo-Like Kinase 2 Signaling. Cells, 9.","DOI":"10.3390\/cells9030740"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ruiz-Pozo, V.A., Tamayo-Trujillo, R., Cadena-Ullauri, S., Frias-Toral, E., Guevara-Ram\u00edrez, P., Paz-Cruz, E., Chapela, S., Montalv\u00e1n, M., Morales-L\u00f3pez, T., and Simancas-Racines, D. (2023). The Molecular Mechanisms of the Relationship between Insulin Resistance and Parkinson\u2019s Disease Pathogenesis. Nutrients, 15.","DOI":"10.3390\/nu15163585"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Galizzi, G., and Di Carlo, M. (2022). Insulin and Its Key Role for Mitochondrial Function\/Dysfunction and Quality Control: A Shared Link between Dysmetabolism and Neurodegeneration. Biology, 11.","DOI":"10.3390\/biology11060943"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"8609213","DOI":"10.1155\/2020\/8609213","article-title":"Molecular Mechanisms Linking Oxidative Stress and Diabetes Mellitus","volume":"2020","author":"Yaribeygi","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.febslet.2007.11.057","article-title":"Inflammation and Insulin Resistance","volume":"582","author":"Olefsky","year":"2008","journal-title":"FEBS Lett."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Tian, Y., Jing, G., Ma, M., Yin, R., and Zhang, M. (2024). Microglial activation and polarization in type 2 diabetes-related cognitive impairment: A focused review of pathogenesis. Neurosci. Biobehav. Rev., 165.","DOI":"10.1016\/j.neubiorev.2024.105848"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/mds.26102","article-title":"The medical treatment of Parkinson disease from James Parkinson to George Cotzias","volume":"30","author":"Fahn","year":"2015","journal-title":"Mov. Disord."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1002\/mds.20324","article-title":"Sydney Multicenter Study of Parkinson\u2019s disease: Non-L-dopa-responsive problems dominate at 15 years","volume":"20","author":"Hely","year":"2005","journal-title":"Mov. Disord."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Agostini, F., Masato, A., Bubacco, L., and Bisaglia, M. (2022). Metformin repurposing for parkinson disease therapy: Opportunities and challenges. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010398"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"a1344","DOI":"10.1136\/bmj.a1344","article-title":"Adherence to Mediterranean diet and health status: Meta-analysis","volume":"337","author":"Sofi","year":"2008","journal-title":"BMJ"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1001\/archneur.65.10.1348","article-title":"Prevalence of vitamin d insufficiency in patients with Parkinson disease and Alzheimer disease","volume":"65","author":"Evatt","year":"2008","journal-title":"Arch. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.2174\/0929867033456558","article-title":"MPP+ Analogs Acting on Mitochondria and Inducing Neuro-Degeneration","volume":"10","author":"Kotake","year":"2003","journal-title":"Curr. Med. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/nm.3596","article-title":"Overcoming Drug Development Bottlenecks with Repurposing: Repurposing biguanides to target energy metabolism for cancer treatment","volume":"20","author":"Pollak","year":"2014","journal-title":"Nat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Zhou, J., Massey, S., Story, D., and Li, L. (2018). Metformin: An Old Drug with New Applications. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19102863"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1007\/s00125-017-4342-z","article-title":"The mechanisms of action of metformin","volume":"60","author":"Rena","year":"2017","journal-title":"Diabetologia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1007\/s00125-006-0141-7","article-title":"Effects of metformin and thiazolidinediones on suppression of hepatic glucose production and stimulation of glucose uptake in type 2 diabetes: A systematic review","volume":"49","author":"Natali","year":"2006","journal-title":"Diabetologia"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/S1734-1140(10)70357-1","article-title":"Quantification of metformin by the HPLC method in brain regions, cerebrospinal fluid and plasma of rats treated with lipopolysaccharide","volume":"62","author":"Suchy","year":"2010","journal-title":"Pharmacol. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.brainres.2012.01.028","article-title":"The effect of metformin on food intake and its potential role in hypothalamic regulation in obese diabetic rats","volume":"1444","author":"Lv","year":"2012","journal-title":"Brain Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1124\/jpet.102.034140","article-title":"Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin","volume":"302","author":"Wang","year":"2002","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1042\/bj3480607","article-title":"Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain","volume":"348","author":"Owen","year":"2000","journal-title":"Biochem. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.cmet.2014.09.018","article-title":"Metformin: From Mechanisms of Action to Therapies","volume":"20","author":"Foretz","year":"2014","journal-title":"Cell Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/s41586-021-04059-0","article-title":"Disruption of mitochondrial complex I induces progressive parkinsonism","volume":"599","author":"Zampese","year":"2021","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Tayara, K., Espinosa-Oliva, A.M., Garc\u00eda-Dom\u00ednguez, I., Ismaiel, A.A., Boza-Serrano, A., Deierborg, T., Machado, A., Herrera, A.J., Venero, J.L., and Pablos, R.M. (2018). de Divergent Effects of Metformin on an Inflammatory Model of Parkinson\u2019s Disease. Front. Cell. Neurosci., 12.","DOI":"10.3389\/fncel.2018.00440"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.taap.2016.03.004","article-title":"Metformin, besides exhibiting strong in vivo anti-inflammatory properties, increases mptp-induced damage to the nigrostriatal dopaminergic system","volume":"298","author":"Ismaiel","year":"2016","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1080\/15376516.2020.1741053","article-title":"Protective effect of metformin against rotenone-induced parkinsonism in mice","volume":"30","author":"Wang","year":"2020","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nrm3311","article-title":"AMPK: A nutrient and energy sensor that maintains energy homeostasis","volume":"13","author":"Hardie","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.cmet.2010.04.001","article-title":"Use of cells expressing gamma subunit variants to identify diverse mechanisms of AMPK activation","volume":"11","author":"Hawley","year":"2010","journal-title":"Cell Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1038\/ncb2329","article-title":"The AMP-activated protein kinase (AMPK) signaling pathway coordinates cell growth, autophagy, & metabolism","volume":"13","author":"Mihaylova","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_40","first-page":"161","article-title":"Targeting AMPK Signaling as a Neuroprotective Strategy in Parkinson\u2019s Disease","volume":"8","author":"Curry","year":"2018","journal-title":"J. Park. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.cmet.2016.09.003","article-title":"Metformin Activates AMPK through the Lysosomal Pathway","volume":"24","author":"Zhang","year":"2016","journal-title":"Cell Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/s41556-020-0461-8","article-title":"Energy-stress-mediated AMPK activation inhibits ferroptosis","volume":"22","author":"Lee","year":"2020","journal-title":"Nat. Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1038\/nm.3372","article-title":"Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin","volume":"19","author":"Fullerton","year":"2013","journal-title":"Nat. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/nm0410-400","article-title":"Diacylglycerol-mediated insulin resistance","volume":"16","author":"Erion","year":"2010","journal-title":"Nat. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.cell.2007.12.035","article-title":"Downregulation of diacylglycerol kinase delta contributes to hyperglycemia-induced insulin resistance","volume":"132","author":"Chibalin","year":"2008","journal-title":"Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/nature11808","article-title":"Biguanides suppress hepatic glucagon signaling by decreasing production of cyclic AMP","volume":"494","author":"Miller","year":"2013","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"10856","DOI":"10.1038\/ncomms10856","article-title":"AMPK antagonizes hepatic glucagon-stimulated cyclic AMP signalling via phosphorylation-induced activation of cyclic nucleotide phosphodiesterase 4B","volume":"7","author":"Johanns","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1016\/S0021-9258(18)64210-3","article-title":"The interaction of energy and electron transfer reactions in mitochondria. I. General properties and nature of the products of succinate-linked reduction of pyridine nucleotide","volume":"236","author":"Chance","year":"1961","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5169","DOI":"10.1016\/S0021-9258(18)99410-X","article-title":"Partial resolution of the enzymes catalyzing oxidative phosphorylation. XV. Reverse electron transfer in the flavin-cytochrome beta region of the respiratory chain of beef heart submitochondrial particles","volume":"242","author":"Hinkle","year":"1967","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1046\/j.0022-3042.2002.00744.x","article-title":"Generation of reactive oxygen species by the mitochondrial electron transport chain","volume":"80","author":"Liu","year":"2002","journal-title":"J. Neurochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s10863-006-9003-8","article-title":"The ROS Production Induced by a Reverse-Electron Flux at Respiratory-Chain Complex 1 is Hampered by Metformin","volume":"38","author":"Batandier","year":"2006","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"120","DOI":"10.2337\/diabetes.55.01.06.db05-0943","article-title":"Activation of AMP-activated protein kinase reduces hyperglycemia-induced mitochondrial reactive oxygen species production and promotes mitochondrial biogenesis in human umbilical vein endothelial cells","volume":"55","author":"Kukidome","year":"2006","journal-title":"Diabetes"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.atherosclerosis.2013.10.025","article-title":"Metformin and liraglutide ameliorate high glucose-induced oxidative stress via inhibition of PKC-NAD(P)H oxidase pathway in human aortic endothelial cells","volume":"232","author":"Batchuluun","year":"2014","journal-title":"Atherosclerosis"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1053\/meta.2003.50093","article-title":"An intracellular modulation of free radical production could contribute to the beneficial effects of metformin towards oxidative stress","volume":"52","author":"Raji","year":"2003","journal-title":"Metabolism"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.metabol.2005.01.029","article-title":"Metformin decreases intracellular production of reactive oxygen species in aortic endothelial cells","volume":"54","author":"Ouslimani","year":"2005","journal-title":"Metabolism"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1046\/j.1463-1326.2000.00089.x","article-title":"Effect of four-week metformin treatment on plasma and erythrocyte antioxidative defense enzymes in newly diagnosed obese patients with type 2 diabetes","volume":"2","year":"2000","journal-title":"Diabetes Obes. Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e929","DOI":"10.1016\/j.wneu.2022.08.121","article-title":"Metformin Attenuates Ferroptosis and Promotes Functional Recovery of Spinal Cord Injury","volume":"167","author":"Wang","year":"2022","journal-title":"World Neurosurg."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"108065","DOI":"10.1016\/j.neuropharm.2020.108065","article-title":"Metformin attenuates cadmium-induced neuronal apoptosis in vitro via blocking ROS-dependent PP5\/AMPK-JNK signaling pathway","volume":"175","author":"Chen","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"16619","DOI":"10.1002\/jcp.28337","article-title":"Metformin protects PC12 cells and hippocampal neurons from H2 O2 -induced oxidative damage through activation of AMPK pathway","volume":"234","author":"Zhao","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"108560","DOI":"10.1016\/j.isci.2023.108560","article-title":"Metformin alleviates hepatic iron overload and ferroptosis through AMPK-ferroportin pathway in HFD-induced NAFLD","volume":"26","author":"Yue","year":"2023","journal-title":"iScience"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Hsu, S.-K., Cheng, K.-C., Mgbeahuruike, M.O., Lin, Y.-H., Wu, C.-Y., Wang, H.-M.D., Yen, C.-H., Chiu, C.-C., and Sheu, S.-J. (2021). New Insight into the Effects of Metformin on Diabetic Retinopathy, Aging and Cancer: Nonapoptotic Cell Death, Immunosuppression, and Effects beyond the AMPK Pathway. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179453"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/nm.4269","article-title":"\u03b1-synuclein toxicity in neurodegeneration: Mechanism and therapeutic strategies","volume":"23","author":"Wong","year":"2017","journal-title":"Nat. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.neures.2019.12.017","article-title":"Neuroprotective effect of metformin on dopaminergic neurodegeneration and \u03b1-synuclein aggregation in C. elegans model of Parkinson\u2019s disease","volume":"162","author":"Saewanee","year":"2021","journal-title":"Neurosci. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e1209","DOI":"10.1038\/cddis.2014.175","article-title":"Metformin lowers Ser-129 phosphorylated \u03b1-synuclein levels via mTOR-dependent protein phosphatase 2A activation","volume":"5","author":"Hettich","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0079-6123(10)83007-9","article-title":"Chapter 7-Role of post-translational modifications in modulating the structure, function and toxicity of \u03b1-synuclein: Implications for Parkinson\u2019s disease pathogenesis and therapies","volume":"Volume 183","author":"Cenci","year":"2010","journal-title":"Progress in Brain Research"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.neuropharm.2017.08.015","article-title":"Metformin lowers \u03b1-synuclein phosphorylation and upregulates neurotrophic factor in the MPTP mouse model of Parkinson\u2019s disease","volume":"125","author":"Katila","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1093\/brain\/awx056","article-title":"Glycation potentiates \u03b1-synuclein-associated neurodegeneration in synucleinopathies","volume":"140","author":"Oliveira","year":"2017","journal-title":"Brain"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1007\/s43440-020-00095-1","article-title":"Metformin protects rotenone-induced dopaminergic neurodegeneration by reducing lipid peroxidation","volume":"72","author":"Ozbey","year":"2020","journal-title":"Pharmacol. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"198","DOI":"10.2337\/diabetes.48.1.198","article-title":"Metformin reduces systemic methylglyoxal levels in type 2 diabetes","volume":"48","author":"Beisswenger","year":"1999","journal-title":"Diabetes"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.neuroscience.2014.07.046","article-title":"Neuroprotective effect of metformin in MPTP-induced Parkinson\u2019s disease in mice","volume":"277","author":"Patil","year":"2014","journal-title":"Neuroscience"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Sun, Y., Bai, Y., Wang, D., Xing, Y., Zhang, T., Wang, W., Zhou, S., Cheng, J., Chang, W., and Kong, X. (2023). Protective effects of metformin on pancreatic \u03b2-cell ferroptosis in type 2 diabetes in vivo. Biomed. Pharmacother., 168.","DOI":"10.1016\/j.biopha.2023.115835"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1016\/j.bbrc.2016.08.124","article-title":"Identification of ACSL4 as a biomarker and contributor of ferroptosis","volume":"478","author":"Yuan","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e001370","DOI":"10.1136\/bmjdrc-2020-001370","article-title":"Association between metformin and neurodegenerative diseases of observational studies: Systematic review and meta-analysis","volume":"8","author":"Ping","year":"2020","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"108173","DOI":"10.1016\/j.neuropharm.2020.108173","article-title":"Metformin regulates astrocyte reactivity in Parkinson\u2019s disease and normal aging","volume":"175","author":"Ryu","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/nrgastro.2015.204","article-title":"Neurogastroenterology: Improving glucose tolerance via the gut-brain axis","volume":"13","author":"Weber","year":"2016","journal-title":"Nat. Rev. Gastroeenterol. Hepatol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1093\/brain\/aws009","article-title":"Parkinson\u2019s disease, insulin resistance and novel agents of neuroprotection","volume":"136","author":"Limousin","year":"2013","journal-title":"Brain"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1146\/annurev-med-042320-014032","article-title":"The Gut-Brain Axis","volume":"73","author":"Mayer","year":"2022","journal-title":"Annu. Rev. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1053\/j.gastro.2007.03.054","article-title":"Biology of Incretins: GLP-1 and GIP","volume":"132","author":"Baggio","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.neuint.2017.02.001","article-title":"Crosstalk of metabolic factors and neurogenic signaling in adult neurogenesis: Implication of metabolic regulation for mental and neurological diseases","volume":"106","author":"Gao","year":"2017","journal-title":"Neurochem. Int."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"5356","DOI":"10.1210\/endo.140.11.7143","article-title":"Glucagon-like peptide-1-(7-36)amide is transformed to glucagon-like peptide-1-(9-36)amide by dipeptidyl peptidase IV in the capillaries supplying the L cells of the porcine intestine","volume":"140","author":"Hansen","year":"1999","journal-title":"Endocrinology"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.brainres.2007.02.043","article-title":"Characterization of brainstem preproglucagon projections to the paraventricular and dorsomedial hypothalamic nuclei","volume":"1149","author":"Vrang","year":"2007","journal-title":"Brain Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.tem.2016.10.001","article-title":"Glucagon-like Peptide-1 and the Central\/Peripheral Nervous System: Crosstalk in Diabetes","volume":"28","author":"Muscogiuri","year":"2017","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.neures.2006.04.008","article-title":"Glucagon-like peptide-1 inhibits LPS-induced IL-1beta production in cultured rat astrocytes","volume":"55","author":"Iwai","year":"2006","journal-title":"Neurosci. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.4103\/1673-5374.332122","article-title":"Parkinson\u2019s disease and diabetes mellitus: Common mechanisms and treatment repurposing","volume":"17","author":"Labandeira","year":"2022","journal-title":"Neural Regen. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1177\/0963689717721234","article-title":"A New Treatment Strategy for Parkinson\u2019s Disease through the Gut\u2013Brain Axis: The Glucagon-Like Peptide-1 Receptor Pathway","volume":"26","author":"Kim","year":"2017","journal-title":"Cell Transpl."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/0014-5793(94)01430-9","article-title":"Tissue-specific expression of the human receptor for glucagon-like peptide-I: Brain, heart and pancreatic forms have the same deduced amino acid sequences","volume":"358","author":"Wei","year":"1995","journal-title":"FEBS Lett."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/361362a0","article-title":"Pancreatic beta-cells are rendered glucose-competent by the insulinotropic hormone glucagon-like peptide-1(7-37)","volume":"361","author":"Holz","year":"1993","journal-title":"Nature"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/(SICI)1096-9861(19990111)403:2<261::AID-CNE8>3.0.CO;2-5","article-title":"Distribution of pre-pro-glucagon and glucagon-like peptide-1 receptor messenger RNAs in the rat central nervous system","volume":"403","author":"Merchenthaler","year":"1999","journal-title":"J. Comp. Neurol."},{"key":"ref_89","first-page":"695","article-title":"Protective properties of GLP-1 and associated peptide hormones in neurodegenerative disorders","volume":"179","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41380-022-01792-4","article-title":"Incretin and insulin signaling as novel therapeutic targets for Alzheimer\u2019s and Parkinson\u2019s disease","volume":"28","author":"Nowell","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Hunter, K., and H\u00f6lscher, C. (2012). Drugs developed to treat diabetes, liraglutide and lixisenatide, cross the blood brain barrier and enhance neurogenesis. BMC Neurosci., 13.","DOI":"10.1186\/1471-2202-13-33"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Salameh, T.S., Rhea, E.M., Talbot, K., and Banks, W.A. (2020). Brain uptake pharmacokinetics of incretin receptor agonists showing promise as Alzheimer\u2019s and Parkinson\u2019s disease therapeutics. Biochem. Pharmacol., 180.","DOI":"10.1016\/j.bcp.2020.114187"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"745","DOI":"10.4103\/1673-5374.249217","article-title":"Repositioning of dipeptidyl peptidase-4 inhibitors and glucagon like peptide-1 agonists as potential neuroprotective agents","volume":"14","author":"Mousa","year":"2019","journal-title":"Neural Regen. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1177\/1479164118788079","article-title":"Neuroprotective effect of glucagon-like peptide-1 receptor agonist is independent of glycaemia normalization in type two diabetic rats","volume":"15","author":"Filchenko","year":"2018","journal-title":"Diab. Vasc. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1002\/jnr.22565","article-title":"Novel GLP-1 mimetics developed to treat type 2 diabetes promote progenitor cell proliferation in the brain","volume":"89","author":"Hamilton","year":"2011","journal-title":"J. Neurosci. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2888","DOI":"10.4161\/cc.8.18.9512","article-title":"Dopaminergic modulation of neurogenesis in the subventricular zone of the adult brain","volume":"8","author":"Barker","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3585","DOI":"10.1210\/endo.136.8.7628397","article-title":"Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV","volume":"136","author":"Kieffer","year":"1995","journal-title":"Endocrinology"},{"key":"ref_98","first-page":"3575","article-title":"Degradation of endogenous and exogenous gastric inhibitory polypeptide in healthy and in type 2 diabetic subjects as revealed using a new assay for the intact peptide","volume":"85","author":"Deacon","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.cmet.2006.10.001","article-title":"GLP-1 receptor activation improves beta cell function and survival following induction of endoplasmic reticulum stress","volume":"4","author":"Yusta","year":"2006","journal-title":"Cell Metab."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Reich, N., and H\u00f6lscher, C. (2022). The neuroprotective effects of glucagon-like peptide 1 in Alzheimer\u2019s and Parkinson\u2019s disease: An in-depth review. Front. Neurosci., 16.","DOI":"10.3389\/fnins.2022.970925"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1073\/pnas.0806720106","article-title":"GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism","volume":"106","author":"Li","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1111\/j.1471-4159.2010.06731.x","article-title":"Enhancing the GLP-1 receptor signaling pathway leads to proliferation and neuroprotection in human neuroblastoma cells","volume":"113","author":"Li","year":"2010","journal-title":"J. Neurochem."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Li, P.-C., Liu, L.-F., Jou, M.-J., and Wang, H.-K. (2016). The GLP-1 receptor agonists exendin-4 and liraglutide alleviate oxidative stress and cognitive and micturition deficits induced by middle cerebral artery occlusion in diabetic mice. BMC Neurosci., 17.","DOI":"10.1186\/s12868-016-0272-9"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.brainres.2011.10.026","article-title":"Repeated administration of exendin-4 reduces focal cerebral ischemia-induced infarction in rats","volume":"1427","author":"Briyal","year":"2012","journal-title":"Brain Res."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Shen, R., Qin, S., Lv, Y., Liu, D., Ke, Q., Shi, C., Jiang, L., Yang, J., and Zhou, Y. (2024). GLP-1 receptor agonist attenuates tubular cell ferroptosis in diabetes via enhancing AMPK-fatty acid metabolism pathway through macropinocytosis. Biochim. Biophys. Acta Mol. Basis Dis., 1870.","DOI":"10.1016\/j.bbadis.2024.167060"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"21513","DOI":"10.3390\/ijms141121513","article-title":"Neuroprotective Effects of Liraglutide for Stroke Model of Rats","volume":"14","author":"Sato","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.neuroscience.2014.09.064","article-title":"Neuroprotective and anti-apoptotic effects of liraglutide in the rat brain following focal cerebral ischemia","volume":"281","author":"Briyal","year":"2014","journal-title":"Neuroscience"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s11064-021-03442-7","article-title":"Liraglutide Alleviates Cognitive Deficit in db\/db Mice: Involvement in Oxidative Stress, Iron Overload, and Ferroptosis","volume":"47","author":"An","year":"2022","journal-title":"Neurochem. Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"8334","DOI":"10.1080\/21655979.2022.2051858","article-title":"Liraglutide attenuates hepatic iron levels and ferroptosis in db\/db mice","volume":"13","author":"Song","year":"2022","journal-title":"Bioengineered"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"3094504","DOI":"10.1155\/2018\/3094504","article-title":"Liraglutide Activates the Nrf2\/HO-1 Antioxidant Pathway and Protects Brain Nerve Cells against Cerebral Ischemia in Diabetic Rats","volume":"2018","author":"Deng","year":"2018","journal-title":"Comput. Intell. Neurosci."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Duarte, A.I., Candeias, E., Alves, I.N., Mena, D., Silva, D.F., Machado, N.J., Campos, E.J., Santos, M.S., Oliveira, C.R., and Moreira, P.I. (2020). Liraglutide Protects Against Brain Amyloid-\u03b21-42 Accumulation in Female Mice with Early Alzheimer\u2019s Disease-Like Pathology by Partially Rescuing Oxidative\/Nitrosative Stress and Inflammation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051746"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Wici\u0144ski, M., Socha, M., Malinowski, B., W\u00f3dkiewicz, E., Walczak, M., G\u00f3rski, K., S\u0142upski, M., and Pawlak-Osi\u0144ska, K. (2019). Liraglutide and its Neuroprotective Properties\u2014Focus on Possible Biochemical Mechanisms in Alzheimer\u2019s Disease and Cerebral Ischemic Events. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051050"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.ejcb.2017.03.004","article-title":"Incretin hormones regulate microglia oxidative stress, survival and expression of trophic factors","volume":"96","author":"Spielman","year":"2017","journal-title":"Eur. J. Cell Biol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S0074-7742(07)82012-5","article-title":"Neuroinflammation in Alzheimer\u2019s Disease and Parkinson\u2019s Disease: Are Microglia Pathogenic in Either Disorder?","volume":"Volume 82","author":"Rogers","year":"2007","journal-title":"International Review of Neurobiology"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1046\/j.1471-4159.2001.00216.x","article-title":"Molecular consequences of activated microglia in the brain: Overactivation induces apoptosis","volume":"77","author":"Liu","year":"2001","journal-title":"J. Neurochem."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2730","DOI":"10.1172\/JCI68295","article-title":"Exenatide and the treatment of patients with Parkinson\u2019s disease","volume":"123","author":"Dickson","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_117","first-page":"337","article-title":"Motor and cognitive advantages persist 12 months after exenatide exposure in Parkinson\u2019s disease","volume":"4","author":"Dickson","year":"2014","journal-title":"J. Park. Dis."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1016\/S0140-6736(17)31585-4","article-title":"Exenatide once weekly versus placebo in Parkinson\u2019s disease: A randomised, double-blind, placebo-controlled trial","volume":"390","author":"Athauda","year":"2017","journal-title":"Lancet"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1111\/ejn.14096","article-title":"Post hoc analysis of the Exenatide-PD trial-Factors that predict response","volume":"49","author":"Athauda","year":"2019","journal-title":"Eur. J. Neurosci."},{"key":"ref_120","first-page":"CD012990","article-title":"GLP-1 receptor agonists for Parkinson\u2019s disease","volume":"7","author":"Mulvaney","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Hogg, E., Wu, T., Bresee, C., Wertheimer, J., Malatt, C., Tan, E., Pomeroy, H., Nuno, M., Wyse, R., and Tagliati, M. (2022). A Phase II, Randomized, Double-Blinded, Placebo-Controlled Trial of Liraglutide in Parkinson\u2019s Disease. SSRN Electron. J.","DOI":"10.2139\/ssrn.4212371"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"e047993","DOI":"10.1136\/bmjopen-2020-047993","article-title":"Exenatide once weekly over 2 years as a potential disease-modifying treatment for Parkinson\u2019s disease: Protocol for a multicentre, randomised, double blind, parallel group, placebo controlled, phase 3 trial: The \u201cExenatide-PD3\u201d study","volume":"11","author":"Vijiaratnam","year":"2021","journal-title":"BMJ Open"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"209ra151","DOI":"10.1126\/scitranslmed.3007218","article-title":"Unimolecular dual incretins maximize metabolic benefits in rodents, monkeys, and humans","volume":"5","author":"Finan","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.neuropharm.2018.02.012","article-title":"Two novel dual GLP-1\/GIP receptor agonists are neuroprotective in the MPTP mouse model of Parkinson\u2019s disease","volume":"133","author":"Feng","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_125","first-page":"523","article-title":"The Novel Dual GLP-1\/GIP Receptor Agonist DA-CH5 Is Superior to Single GLP-1 Receptor Agonists in the MPTP Model of Parkinson\u2019s Disease","volume":"10","author":"Zhang","year":"2020","journal-title":"J. Park. Dis."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/S1537-1891(02)00202-1","article-title":"Drug delivery to brain via the blood-brain barrier","volume":"38","author":"Scherrmann","year":"2002","journal-title":"Vascul. Pharmacol."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Guo, X., Lei, M., Zhao, J., Wu, M., Ren, Z., Yang, X., Ouyang, C., Liu, X., Liu, C., and Chen, Q. (2023). Tirzepatide ameliorates spatial learning and memory impairment through modulation of aberrant insulin resistance and inflammation response in diabetic rats. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1146960"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"112308","DOI":"10.1016\/j.intimp.2024.112308","article-title":"The potential role of Tirzepatide as adjuvant therapy in countering colistin-induced nephro and neurotoxicity in rats via modulation of PI3K\/p-Akt\/GSK3-\u03b2\/NF-kB p65 hub, shielding against oxidative and endoplasmic reticulum stress, and activation of p-CREB\/BDNF\/TrkB cascade","volume":"135","author":"Hassan","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"9184","DOI":"10.1080\/21655979.2022.2051859","article-title":"Novel dual glucagon-like peptide-1\/ glucose-dependent insulinotropic polypeptide receptor agonist attenuates diabetes and myocardial injury through inhibiting hyperglycemia, inflammation and oxidative stress in rodent animals","volume":"13","author":"Wang","year":"2022","journal-title":"Bioengineered"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"107813","DOI":"10.1016\/j.neuropharm.2019.107813","article-title":"Neuroprotective and restorative properties of the GLP-1\/GIP dual agonist DA-JC1 compared with a GLP-1 single agonist in Alzheimer\u2019s disease","volume":"162","author":"Salles","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1021\/acsptsci.9b00003","article-title":"Incretin Mimetics as Rational Candidates for the Treatment of Traumatic Brain Injury","volume":"2","author":"Glotfelty","year":"2019","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"113113","DOI":"10.1016\/j.expneurol.2019.113113","article-title":"Neurotrophic and neuroprotective effects of a monomeric GLP-1\/GIP\/Gcg receptor triagonist in cellular and rodent models of mild traumatic brain injury","volume":"324","author":"Li","year":"2020","journal-title":"Exp. Neurol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1210\/er.2014-1035","article-title":"Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors","volume":"35","author":"Mulvihill","year":"2014","journal-title":"Endocr. Rev."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"11994","DOI":"10.18632\/aging.206074","article-title":"Association between dipeptidyl peptidase-4 inhibitor use and risk of Parkinson\u2019s disease among patients with diabetes mellitus: A retrospective cohort study","volume":"16","author":"Huang","year":"2024","journal-title":"Aging"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1463-1326.2010.01306.x","article-title":"Dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes: A comparative review","volume":"13","author":"Deacon","year":"2011","journal-title":"Diabetes Obes. Metab."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1111\/jnc.13087","article-title":"Neuroprotective effects of vildagliptin in rat rotenone Parkinson\u2019s disease model: Role of RAGE-NF\u03baB and Nrf2-antioxidant signaling pathways","volume":"133","author":"Abdelsalam","year":"2015","journal-title":"J. Neurochem."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"247","DOI":"10.2147\/TCRM.S30071","article-title":"Profile of vildagliptin in type 2 diabetes: Efficacy, safety, and patient acceptability","volume":"9","author":"Pan","year":"2013","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1210\/en.2011-1712","article-title":"Impact of the dipeptidyl peptidase-4 inhibitor vildagliptin on glucose tolerance and \u03b2-cell function and mass in insulin receptor substrate-2-knockout mice fed a high-fat diet","volume":"153","author":"Sato","year":"2012","journal-title":"Endocrinology"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/dom.12005","article-title":"Vildagliptin preserves the mass and function of pancreatic \u03b2 cells via the developmental regulation and suppression of oxidative and endoplasmic reticulum stress in a mouse model of diabetes","volume":"15","author":"Hamamoto","year":"2013","journal-title":"Diabetes Obes. Metab."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1530\/JOE-12-0521","article-title":"DPP-4 inhibitors improve cognition and brain mitochondrial function of insulin-resistant rats","volume":"218","author":"Pintana","year":"2013","journal-title":"J. Endocrinol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1111\/ejn.12088","article-title":"DPP4-inhibitor improves neuronal insulin receptor function, brain mitochondrial function and cognitive function in rats with insulin resistance induced by high-fat diet consumption","volume":"37","author":"Pipatpiboon","year":"2013","journal-title":"Eur. J. Neurosci."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.metabol.2014.08.006","article-title":"Dipeptidyl peptidase-4 inhibitor, vildagliptin, inhibits pancreatic beta cell apoptosis in association with its effects suppressing endoplasmic reticulum stress in db\/db mice","volume":"64","author":"Wu","year":"2015","journal-title":"Metabolism"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1089\/ars.2014.5851","article-title":"Endoplasmic Reticulum Stress and Oxidative Stress in Cell Fate Decision and Human Disease","volume":"21","author":"Cao","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1093\/abbs\/gmu048","article-title":"New insights into the roles of CHOP-induced apoptosis in ER stress","volume":"46","author":"Li","year":"2014","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.phrs.2011.02.003","article-title":"Vildagliptin blocks vascular injury in thoracic aorta of diabetic rats by suppressing advanced glycation end product-receptor axis","volume":"63","author":"Matsui","year":"2011","journal-title":"Pharmacol. Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.neuropharm.2014.10.007","article-title":"Saxagliptin: A novel antiparkinsonian approach","volume":"89","author":"Nassar","year":"2015","journal-title":"Neuropharmacology"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s10787-017-0331-6","article-title":"Sitagliptin and liraglutide reversed nigrostriatal degeneration of rodent brain in rotenone-induced Parkinson\u2019s disease","volume":"25","author":"Badawi","year":"2017","journal-title":"Inflammopharmacology"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.nbd.2011.12.043","article-title":"Sitagliptin increases tau phosphorylation in the hippocampus of rats with type 2 diabetes and in primary neuron cultures","volume":"46","author":"Kim","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Dom\u00ednguez Avila, J.A., Rodrigo Garc\u00eda, J., Gonz\u00e1lez Aguilar, G.A., and De la Rosa, L.A. (2017). The Antidiabetic Mechanisms of Polyphenols Related to Increased Glucagon-Like Peptide-1 (GLP1) and Insulin Signaling. Molecules, 22.","DOI":"10.3390\/molecules22060903"},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Ogura, J., and Yamaguchi, H. (2022). The Effectiveness of Antidiabetic Drugs in Treating Dementia: A Peek into Pharmacological and Pharmacokinetic Properties. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23126542"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1002\/mds.26734","article-title":"Reduced incidence of Parkinson\u2019s disease after dipeptidyl peptidase-4 inhibitors-A nationwide case-control study","volume":"31","author":"Svenningsson","year":"2016","journal-title":"Mov. Disord."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.1093\/brain\/awaa262","article-title":"Diabetes medications and risk of Parkinson\u2019s disease: A cohort study of patients with diabetes","volume":"143","author":"Brauer","year":"2020","journal-title":"Brain"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1093\/brain\/awab015","article-title":"Beneficial effects of dipeptidyl peptidase-4 inhibitors in diabetic Parkinson\u2019s disease","volume":"144","author":"Jeong","year":"2021","journal-title":"Brain"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"140","DOI":"10.2337\/dc14-2441","article-title":"Management of Hyperglycemia in Type 2 Diabetes, 2015: A Patient-Centered Approach: Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes","volume":"38","author":"Inzucchi","year":"2014","journal-title":"Diabetes Care"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/bs.irn.2020.02.010","article-title":"Antidiabetic drugs for Alzheimer\u2019s and Parkinson\u2019s diseases: Repurposing insulin, metformin, and thiazolidinediones","volume":"155","author":"Cardoso","year":"2020","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_156","first-page":"683","article-title":"Management of type 2 diabetes mellitus. Role of thiazolidinediones","volume":"51","author":"Noble","year":"2005","journal-title":"Can. Fam. Physician"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.freeradbiomed.2016.06.023","article-title":"PPAR\u03b3 as a therapeutic target to rescue mitochondrial function in neurological disease","volume":"100","author":"Corona","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Liu, W., Xiong, Z., Fu, T., Yang, J., Zou, J., Wu, Y., Kuang, L., Wang, Q., Li, S., and Le, A. (2024). Regulation of renal ischemia-reperfusion injury and tubular epithelial cell ferroptosis by ppar\u03b3 m6a methylation: Mechanisms and therapeutic implications. Biol. Direct, 19.","DOI":"10.1186\/s13062-024-00515-9"},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Lai, W., Yu, L., and Deng, Y. (2024). PPAR\u03b3 alleviates preeclampsia development by regulating lipid metabolism and ferroptosis. Commun. Biol., 7.","DOI":"10.1038\/s42003-024-06063-2"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"175175","DOI":"10.1016\/j.ejphar.2022.175175","article-title":"Proteomic analysis reveals that ACSL4 activation during reflux esophagitis contributes to ferroptosis-mediated esophageal mucosal damage","volume":"931","author":"Liu","year":"2022","journal-title":"Eur. J. Pharmacol."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Wang, Y., Zhang, M., Bi, R., Su, Y., Quan, F., Lin, Y., Yue, C., Cui, X., Zhao, Q., and Liu, S. (2022). ACSL4 deficiency confers protection against ferroptosis-mediated acute kidney injury. Redox Biol., 51.","DOI":"10.1016\/j.redox.2022.102262"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"16262","DOI":"10.1096\/fj.202001758R","article-title":"Inhibition of ACSL4 attenuates ferroptotic damage after pulmonary ischemia-reperfusion","volume":"34","author":"Xu","year":"2020","journal-title":"FASEB J."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1038\/s41418-019-0299-4","article-title":"Ischemia-induced ACSL4 activation contributes to ferroptosis-mediated tissue injury in intestinal ischemia\/reperfusion","volume":"26","author":"Li","year":"2019","journal-title":"Cell Death Differ"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"927","DOI":"10.3233\/JAD-230593","article-title":"Multi-Target Neuroprotection of Thiazolidinediones on Alzheimer\u2019s Disease via Neuroinflammation and Ferroptosis","volume":"96","author":"Yang","year":"2023","journal-title":"J. Alzheimers Dis."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1046\/j.1471-4159.2002.00990.x","article-title":"Protective action of the peroxisome proliferator-activated receptor-gamma agonist pioglitazone in a mouse model of Parkinson\u2019s disease","volume":"82","author":"Breidert","year":"2002","journal-title":"J. Neurochem."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1046\/j.1471-4159.2003.02210.x","article-title":"Protection by pioglitazone in the MPTP model of Parkinson\u2019s disease correlates with I kappa B alpha induction and block of NF kappa B and iNOS activation","volume":"88","author":"Dehmer","year":"2004","journal-title":"J. Neurochem."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1111\/j.1471-4159.2006.04327.x","article-title":"Inflammation induces mitochondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system","volume":"100","author":"Hunter","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.bbr.2008.10.010","article-title":"Beneficial effects of pioglitazone on cognitive impairment in MPTP model of Parkinson\u2019s disease","volume":"197","author":"Kumar","year":"2009","journal-title":"Behav. Brain Res."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.tiv.2011.02.004","article-title":"Double antioxidant activities of rosiglitazone against high glucose-induced oxidative stress in hepatocyte","volume":"25","author":"Wang","year":"2011","journal-title":"Toxicol. In Vitro"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.bbrc.2005.11.177","article-title":"Rosiglitazone protects human neuroblastoma SH-SY5Y cells against acetaldehyde-induced cytotoxicity","volume":"340","author":"Jung","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.redox.2017.06.009","article-title":"The SGLT2 inhibitor empagliflozin improves the primary diabetic complications in ZDF rats","volume":"13","author":"Steven","year":"2017","journal-title":"Redox Biol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"3231","DOI":"10.1002\/jcp.26760","article-title":"Sodium-glucose cotransporter inhibitors and oxidative stress: An update","volume":"234","author":"Yaribeygi","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1124\/jpet.118.253666","article-title":"Empagliflozin, an SGLT2 Inhibitor, Reduced the Mortality Rate after Acute Myocardial Infarction with Modification of Cardiac Metabolomes and Antioxidants in Diabetic Rats","volume":"368","author":"Oshima","year":"2019","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"542042","DOI":"10.1155\/2012\/542042","article-title":"Sodium-glucose cotransporter inhibition prevents oxidative stress in the kidney of diabetic rats","volume":"2012","author":"Osorio","year":"2012","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Terami, N., Ogawa, D., Tachibana, H., Hatanaka, T., Wada, J., Nakatsuka, A., Eguchi, J., Horiguchi, C.S., Nishii, N., and Yamada, H. (2014). Long-term treatment with the sodium glucose cotransporter 2 inhibitor, dapagliflozin, ameliorates glucose homeostasis and diabetic nephropathy in db\/db mice. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0100777"},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Tsai, K.-F., Chen, Y.-L., Chiou, T.T.-Y., Chu, T.-H., Li, L.-C., Ng, H.-Y., Lee, W.-C., and Lee, C.-T. (2021). Emergence of SGLT2 Inhibitors as Powerful Antioxidants in Human Diseases. Antioxidants, 10.","DOI":"10.3390\/antiox10081166"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"176934","DOI":"10.1016\/j.ejphar.2024.176934","article-title":"Effects of empagliflozin and dapagliflozin on serum humanin, MOTS-c levels, nitrosative stress, and ferroptosis parameters in diabetic patients with heart failure","volume":"982","author":"Asil","year":"2024","journal-title":"Eur. J. Pharmacol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.freeradbiomed.2017.01.035","article-title":"Dapagliflozin, a selective SGLT2 Inhibitor, attenuated cardiac fibrosis by regulating the macrophage polarization via STAT3 signaling in infarcted rat hearts","volume":"104","author":"Lee","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_179","first-page":"e58536","article-title":"A Study to Evaluate the Effect of Sodium-Glucose Co-transporter 2 (SGLT2) Inhibitors on Oxidative Stress Parameters in Type 2 Diabetes Mellitus Patients","volume":"16","author":"Sharma","year":"2024","journal-title":"Cureus"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"297","DOI":"10.2337\/dc22-1705","article-title":"Association of Sodium-Glucose Cotransporter 2 Inhibitors with Time to Dementia: A Population-Based Cohort Study","volume":"46","author":"Wu","year":"2023","journal-title":"Diabetes Care"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"e209805","DOI":"10.1212\/WNL.0000000000209805","article-title":"SGLT2 Inhibitor Use and Risk of Dementia and Parkinson Disease Among Patients with Type 2 Diabetes","volume":"103","author":"Kim","year":"2024","journal-title":"Neurology"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"e3624","DOI":"10.1002\/brb3.3624","article-title":"Sodium-glucose cotransporter 1\/2 inhibition and risk of neurodegenerative disorders: A Mendelian randomization study","volume":"14","author":"Liu","year":"2024","journal-title":"Brain Behav."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.2337\/dc19-0760","article-title":"Association Between Glycemic Status and the Risk of Parkinson Disease: A Nationwide Population-Based Study","volume":"43","author":"Rhee","year":"2020","journal-title":"Diabetes Care"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"4193","DOI":"10.1007\/s10072-023-06965-9","article-title":"Do oral antidiabetic medications alter the risk of Parkinson\u2019s disease? An updated systematic review and meta-analysis","volume":"44","author":"Xie","year":"2023","journal-title":"Neurol. Sci."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1089\/rej.2023.0010","article-title":"Acarbose Mitigates Age-Dependent Alterations in Erythrocyte Membrane Transporters During Aging in Rats","volume":"26","author":"Arya","year":"2023","journal-title":"Rejuvenation Res."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1089\/rej.2022.0032","article-title":"Acarbose, an \u03b1-Glucosidase Inhibitor, Maintains Altered Redox Homeostasis During Aging by Targeting Glucose Metabolism in Rat Erythrocytes","volume":"26","author":"Arya","year":"2023","journal-title":"Rejuvenation Res."},{"key":"ref_187","doi-asserted-by":"crossref","unstructured":"Chan, K.-C., Yu, M.-H., Lin, M.-C., Huang, C.-N., Chung, D.-J., Lee, Y.-J., Wu, C.-H., and Wang, C.-J. (2016). Pleiotropic effects of acarbose on atherosclerosis development in rabbits are mediated via upregulating AMPK signals. Sci. Rep., 6.","DOI":"10.1038\/srep38642"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1111\/1753-0407.12232","article-title":"Acarbose treatment affects the serum levels of inflammatory cytokines and the gut content of bifidobacteria in Chinese patients with type 2 diabetes mellitus","volume":"7","author":"Su","year":"2015","journal-title":"J. Diabetes"},{"key":"ref_189","doi-asserted-by":"crossref","unstructured":"NINDS (2015). Exploratory Trials in Parkinson Disease (NET-PD) FS-ZONE Investigators Pioglitazone in early Parkinson\u2019s disease: A phase 2, multicentre, double-blind, randomised trial. Lancet Neurol., 14, 795\u2013803.","DOI":"10.1016\/S1474-4422(15)00144-1"},{"key":"ref_190","first-page":"2838669","article-title":"Investigation of the Possible Correlation between Idiopathic Parkinson\u2019s Disease and Diabetes Mellitus in Egyptian Patients: A Pilot Study","volume":"2021","author":"Hamed","year":"2021","journal-title":"Neurol. Res. Int."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/4\/1516\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:31:24Z","timestamp":1760027484000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/4\/1516"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,11]]},"references-count":190,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["ijms26041516"],"URL":"https:\/\/doi.org\/10.3390\/ijms26041516","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,11]]}}}